1. Prescribing in Dementia

2. Plan What to prescribe? When to prescribe? How to review? Who to review?

3. Toolkit Cognitive function enhancers – Acetyl Choline-Esterase Inhibitors – Memantine Antipsychotics Others – Antidepressants – Anxiolytics – Anticonvulsants

4. Cognitive function enhancers SIGN Guideline (http://www.sign.ac.uk/pdf/sign86.pdf)http://www.sign.ac.uk/pdf/sign86.pdf NICE pathway (http://pathways.nice.org.uk/pathways/deme ntia)http://pathways.nice.org.uk/pathways/deme ntia Local practice

5. Cognitive function enhancers Improvements in cognitive function Helps in managing “behaviour that is challenging” though evidence base is limited (J Rodda, S Morgan & Z Walker International Psychogeriatrics, 21, pp 813-824. doi:10.1017/S1041610209990354) Delays institutionalisation

6. Kaplan-Meier plot of time to nursing home admission among patients with Alzheimer's disease (A) taking and (B) not taking CEIs. Lopez O L et al. J Neurol Neurosurg Psychiatry 2002;72:310-314 ©2002 by BMJ Publishing Group Ltd

7. When to prescribe? Following conditions – Dementia in Alzheimer’s disease – Mixed AD & vascular dementia – Dementia in Lewy Body Disease – Dementia in Parkinson’s disease At earliest possible opportunity After a discussion with the person with dementia and their families

8. Before prescribing Bloods – Renal functions – Liver functions ECG to rule out heart blocks (2 nd degree & worse), prolonged QT c intervals

9. When to review? No special requirements Considerable experience gained over the recent years Initial review after about a month followed by another in 6 months – Compliance – Adverse effects Further annual reviews adequate, unless there are issues

10. Who to review? Regular reviews in Old Age Psychiatry, currently not routine practice Flexible arrangements as per clinical requirements appropriate Could be part of annual reviews in primary care

11. Antipsychotics RCPsych Paper on antipsychotics in dementia

12. Typical antipsychotics Eg.: Haloperidol Systematic review (Lanctot JCP 1998) Therapeutic effect was 26 %(CI 14-38%) Adverse effects 25 % (13-37%) Chance of benefit or harm equal

13. Atypical Antipsychotics Systematic review (Schneider AJGP 2006) Aripiprazole Olanzapine Quetiapine Risperidone

14. EFEECT SIZES (WMD) Aripiprazole -3.63 on NPI -4.05 on CMAI Risperidone -3.0 -1.48

15. EFFICACY Meta analysis Aripiprazole (3 studies)-efficacy Risperidone (4 studies)—efficacy Olanzapine (3 studies)-no efficacy Quetiapine-(0 studies)-??? Beneficial effects smaller

16. Adverse effects Parkinsonism Akathisia Tardive dyskinesia Sedation Conduction Postural hypotension Falls Cognitive decline

17. CATIE-AD NEJM 2006 Large pragmatic RCT 421 Ops (36/52) AD with psychosis, agitation or aggression Olanzapine (5.5mg) v quetiapine (55 mg) v Risperidone 1mg v placebo Discontinuation due to lack of efficacy – Favoured Olanzapine and risperidone Discontinuation due to AEs – Favoured placebo Conclusion: small benefits offset by AE’s

18. UK CSM 2004 4 RCT’s Risperidone (0.5-2 mg), 8-12 wks 33 (3.3%) cerebro-vascular adverse events Risperidone v 8 (1.2%) placebo Odds Ratio 3.32 (95 % CI: 1.43-7.70) No significant difference in overall mortality

19. FDA 2005 17 studies> 5000 elderly dementia patients taking risperidone, olanzapine, aripiprazole or quetiapine 1.7 fold increase in mortality for atypicals— class effect Causes: cardiac or infections Black box warnings also for clozapine and ziprasidone

20. Mortality and antipsychotics (cohort studies) Wang 2005-typicals worse than atypicals in older people Gill 2007-atypicals increased risk in elderly, demented, typicals worse than atypicals Kales 2007-antipsychotics worse than other medication in dementia, no difference between typicals and atypicals Schneeweiss 2007—typicals worse than atypicals in older people

21. Efficacy of Antipsychotics Overall there is evidence for efficacy for both typical and atypical antipsychotic Effect sizes are however small Placebo response is high Aggressive behaviour seems to respond best Severly impaired people respond better Response tend to occur early Best evidence of efficacy for risperidone Substantial risk of disbenefit Association with serious AE’s

22. Local recommendations Initiation after careful consideration of risks & response to non-pharmacological treatments Smallest possible dose, titrated gradually upwards Review weekly to fortnightly Discontinue, if appropriate, in 6-12 weeks